A genome-wide association study of bronchodilator response in asthmatics
A genome-wide association study of bronchodilator response in asthmatics
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DOI：
10.1038/tpj.2013.5
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发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Tantisira, K. G.
中科院分区：
文献类型：
--
作者：
Duan, Q. L.;Lasky-Su, J.;Tantisira, K. G.
哮喘患者对β 2受体激动剂反应的气道阻塞可逆性差异很大，这部分归因于遗传因素。在对吸入沙丁胺醇的急性支气管扩张剂反应（BDR）的全基因组关联研究中，使用5种统计模型对来自儿童哮喘管理项目的403名白色三人组中的534 290个单核苷酸多态性（SNP）进行了检测，以确定最可靠的遗传关联。主要复制阶段包括三项哮喘试验中的1397个多态性（汇总n = 764）。第二个复制阶段在另外三个哮喘人群中测试了13个SNP（n = 241、n = 215和n = 592）。10号染色体上的一个基因间SNP rs 11252394，接近几个优秀的生物学候选者，在初级复制试验中显著复制（P = 1.98 x 10（-7））。胶原（COL 22 A1）基因座中的内含子SNP（rs6988229）也提供了强复制信号（P = 8.51 x 10（-6））。本研究应用了一种强有力的方法来检测BDR的遗传基础，并确定了与哮喘患者的这种药物反应相关的新基因座。
Reversibility of airway obstruction in response to beta(2)-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n = 764). The second replication phase tested 13 SNPs in three additional asthma populations (n = 241, n = 215 and n = 592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P = 1.98 x 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P = 8.51 x 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.